WIN 55,212-2 Reverted Pilocarpine-Induced Status Epilepticus Early Changes of the Interaction among 5-HT2C/NMDA/CB1 Receptors in the Rat Hippocampus

The molecular basis for temporal lobe epileptogenesis (TLE) remains poorly defined as of yet. Recent evidence shows that serotonin2C receptors (5-HT2CRs), NR2A and NR2B subunit-containing NMDARs and cannabinoid 1Rs (CB1Rs) may be involved in the progression of the epileptic disorders. Moreover, CB1R activation has been reported to modulate the activity of 5-HT2C and NMDARs. Here, we treated Sprague-Dawley rats with the pro-convulsant agent pilocarpine (PILO) to induce status epilepticus (SE) in order to study the effect, with regards to receptor signalling and their interactions, of the pre-activation of the CB1Rs on early changes that occur 24 h from the initial insult in the hippocampus. Pretreatment with the synthetic CB1/2R agonist WIN55,212-2 (2 mg/kg, i.p.) counteracted PILO-induced 5-HT2CR downregulation. Moreover, WIN55,212-2 uncoupled PILO-induced 5-HT2CR:NR2A and prevented NR2ATyr 1325 phosphorylation indirectly since no 5-HT2CR:CB1R interactions were observed. WIN55,212-2 treatment also prevent...